The present invention relates to a biomaterial for the culture of cells and/or tissue consisting of cells, based on a polymeric carrier, which contains at least one crosslinked hydrophilic polymer.
Said biomaterials are used in the prior art for example as so-called drug-release materials, as implants, as tissue-forming matrixes or as materials for cell culture, and are often also called “hydrogels”. These biomaterials are usually employed for therapeutic purposes or for biological basic research, because owing to their variable biophysical and biochemical properties they represent valuable tools in regenerative medicine and in “tissue engineering”, and in general cell culture.
With these biomaterials it is therefore possible for example to restore the structure and function of degenerated or damaged tissue, when they are loaded with cells and then implanted, and thus subsequently promote tissue morphogenesis, or if, not loaded with cells, they are implanted in places where, through the growing-in of cells and optionally their differentiation, they promote the formation of new tissue in situ.
As already mentioned, another main application of biomaterials based on natural or synthetic materials is in analytical cell culture applications, by which for example the mechanism of action of biofactors on cells can be investigated.
Various biomaterials based on natural or artificial materials with various properties are known in the prior art, which generally, depending on the desired field of application, are characterized by adequate mechanical stability, elasticity, and resistance to degradation, and above all are nontoxic. Preparations of collagen I are frequently used materials of natural origin. This hydrophilic protein contains regions that react with cells, for example adhesion signals, signals for the proteolytic cleavage of collagen I, or for cell differentiation. These signals and the three-dimensional nature of cultivation contribute to cells in these collagen gels behaving more naturally than in conventional two-dimensional culture on surfaces of culture vessels.
For a better understanding of the functioning of these signals, it is necessary to use biomaterials in which the type and number of signal groups can be controlled, i.e., a biomaterial which does not damage the cells and at first does not carry any signals and is therefore neutral to cells, and which can be modified with signal groups.
In the prior art, see, e.g., Hersel, et al., Biomaterials 24 (2003) 4385-4415; and Lutolf and Hubbell, Nature Biotechnology, 23 (2005) 47-66, as a general rule polyethylene glycol—hereinafter generally abbreviated with PEG—is used as such a polymer that is neutral to cells, as it is nontoxic, it is not bound by cells and is hydrophilic. However, because linear PEG can only be modified at its two ends, and because for the formation of a crosslinked gel at least one reactant must bear at least three reactive groups, on the one hand peptides, which bear at least three reactive groups, are used for crosslinking, or alternatively branched PEG is used, which for example possesses four modifiable ends.
However, the polymers or hydrogels known in the prior art have the disadvantage that the production/isolation of the peptides used for crosslinking is difficult and expensive, and so too is the production of branched PEG. Another disadvantage is that the production of gels from reactants with three or four reactive groups per molecule requires very careful work, because for gel formation all the reactants must be in the correct proportions.
The approaches known in the prior art are therefore disadvantageous for the development of reagents for cell and tissue culture.